...stribution, and reproduction in any medium, provided the original work is properly cited.W250 Nucleic Acids Research, 2011, Vol. 39, Web Server issue small-molecule docking [e.g. Autodock (21), DOCK =-=(22)-=-, PatchDock (18), ParDock (23), MEDdock (24) and others]. These servers, however, are suitable for molecules with a limited number of rotatable bonds only, and therefore not applicable to peptides, wh...

"... The importance of binding site plasticity in protein– ligand interactions is well-recognized, and so are the difficulties in predicting the nature and the degree of this plasticity by computational means. To assist in understanding the flexible protein–ligand interactions, we constructed the Pocketo ..."

The importance of binding site plasticity in protein– ligand interactions is well-recognized, and so are the difficulties in predicting the nature and the degree of this plasticity by computational means. To assist in understanding the flexible protein–ligand interactions, we constructed the Pocketome, an en-cyclopedia of about one thousand experimentally solved conformational ensembles of druggable binding sites in proteins, grouped by location and consistent chain/cofactor composition. The multi-plicity of pockets within the ensembles adds an extra, fourth dimension to the Pocketome entry data. Within each ensemble, the pockets were care-fully classified by the degree of their pairwise simi-larity and compatibility with different ligands. The core of the Pocketome is derived regularly and auto-matically from the current releases of the Protein Data Bank and the Uniprot Knowledgebase; this core is complemented by entries built from manually provided seed ligand locations. The Pocketome website (www.pocketome.org) allows searching for the sites of interest, analysis of con-formational clusters, important residues, binding compatibility matrices and interactive visualization of the ensembles using the ActiveICM web browser plugin. The Pocketome collection can be used to build multi-conformational docking and 3D activity models as well as to design cross-docking and virtual ligand screening benchmarks.

... thus the others are not easily practicable for non-expert scientists. Among web servers, some are dedicated to the virtual screening by docking: DOCK Blaster (http://blaster.docking.org/start.shtml) =-=(23)-=-, TarFisDock (http://www.dddc.ac.cn/tarfisdock/) (24) or the SCFBIO server (http://www.scfbio-iitd.res .in/bioinformatics/drugdesign.htm), but they only screen existing, commercial or uploaded, librar...

"... Biomedical applications have become increasingly complex, and they often require large-scale highperformance computing resources with a large number of processors and memory. The complexity of application deployment and the advances in cluster, grid and cloud computing require new modes of support f ..."

Biomedical applications have become increasingly complex, and they often require large-scale highperformance computing resources with a large number of processors and memory. The complexity of application deployment and the advances in cluster, grid and cloud computing require new modes of support for biomedical research. Scientific Software as a Service (sSaaS) enables scalable and transparent access to biomedical applications through simple standards-based Web interfaces. Towards this end, we built a production web server

...ctions, such as AlignAce (25) as opposed to MEME in motif discovery; use of semi-empirical quantum-chemical techniques (26) as opposed to PDB2PQR or AutoDockTools in partical charge calculation; Dock =-=(27)-=- as opposed to AutoDock in docking; webPIPSA (28) as opposed to APBS in electrostatics analysis, may be coupled in workflows or compared for consensus. Users are encouraged to study the original refer...

"... Open screening endeavors play and will play a key role to facilitate the identification of new bioac-tive compounds in order to foster innovation and to improve the effectiveness of chemical biology and drug discovery processes. In this line, we de-veloped the new web server MTiOpenScreen dedi-cated ..."

Open screening endeavors play and will play a key role to facilitate the identification of new bioac-tive compounds in order to foster innovation and to improve the effectiveness of chemical biology and drug discovery processes. In this line, we de-veloped the new web server MTiOpenScreen dedi-cated to small molecule docking and virtual screen-ing. It includes two services, MTiAutoDock and MTiOpenScreen, allowing performing docking into a user-defined binding site or blind docking us-ing AutoDock 4.2 and automated virtual screening with AutoDock Vina. MTiOpenScreen provides valu-able starting collections for screening, two in-house prepared drug-like chemical libraries containing 150 000 PubChem compounds: the Diverse-lib contain-ing diverse molecules and the iPPI-lib enriched in molecules likely to inhibit protein–protein interac-tions. In addition, MTiOpenScreen offers users the possibility to screen up to 5000 small molecules se-lected outside our two libraries. The predicted bind-ing poses and energies of up to 1000 top ranked ligands can be downloaded. In this way, MTiOpen-Screen enables researchers to apply virtual screen-ing using different chemical libraries on traditional or more challenging protein targets such as protein– protein interactions. The MTiOpenScreen web server is free and open to all users at

...st for docking web servers has emerged recently, as can be seen through the growing list of similar web services currently available, such as DockingServer (http://www.dockingserver.com/web), Blaster =-=(18)-=-, DockingAtUTMB (http://docking.utmb.edu/), Pardock (http://www.scfbio-iitd.res.in/dock/pardock.jsp), PatchDock (http://bioinfo3d.cs.tau.ac.il/PatchDock/), MetaDock (http://dock.bioinfo.pl/), PPDock (...

"... Background:GAT-2 is physiologically andpharmacologically important for regulating peripheralGABAergicmechanisms. Results:We identify GAT-2 ligands, including drugs, metabolites, and fragments, using comparative modeling, virtual screen-ing, and experiments. Conclusion:GAT-2 is a high selectivity/low ..."

Background:GAT-2 is physiologically andpharmacologically important for regulating peripheralGABAergicmechanisms. Results:We identify GAT-2 ligands, including drugs, metabolites, and fragments, using comparative modeling, virtual screen-ing, and experiments. Conclusion:GAT-2 is a high selectivity/low affinity transporter that is resistant to inhibition by typical GABAergic inhibitors. Significance:Our results explain pharmacological and physiological effects of GAT-2 ligands and identify specificity determi-nants in the SLC6 family. The solute carrier 6 (SLC6) is a family of ion-dependent trans-porters that mediate uptake into the cell of osmolytes such as neurotransmitters and amino acids. Four SLC6members trans-port GABA, a key neurotransmitter that triggers inhibitory sig-naling pathways via various receptors (e.g., GABAA). TheGABA transporters (GATs) regulate the concentration of GABA avail-able for signaling and are thus targeted by a variety of anticon-vulsant and relaxant drugs. Here, we characterize GAT-2, a transporter that plays a role in peripheral GABAergic mecha-

"... *S Supporting Information ABSTRACT: Most libraries for fragment-based drug discov-ery are restricted to 1,000−10,000 compounds, but over 500,000 fragments are commercially available and potentially accessible by virtual screening. Whether this larger set would increase chemotype coverage, and whethe ..."

*S Supporting Information ABSTRACT: Most libraries for fragment-based drug discov-ery are restricted to 1,000−10,000 compounds, but over 500,000 fragments are commercially available and potentially accessible by virtual screening. Whether this larger set would increase chemotype coverage, and whether a computational screen can pragmatically prioritize them, is debated. To investigate this question, a 1281-fragment library was screened by nuclear magnetic resonance (NMR) against AmpC β-lactamase, and hits were confirmed by surface plasmon resonance (SPR). Nine hits with novel chemotypes were confirmed biochemically with KI values from 0.2 to low mM. We also computationally docked 290,000 purchasable fragments with chemotypes unrepresented in the empirical library, finding 10 that had KI values from 0.03 to low mM. Though less novel than those discovered by NMR, the docking-derived fragments filled chemotype holes from the empirical library. Crystal structures of nine of the fragments in complex with AmpC β-lactamase revealed new binding sites and explained the relatively high affinity of the docking-derived fragments. The existence of